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Position
Emission Tomography or PET scanning--one of several new imaging
techniques--tracks the course of high energy, very short-lived
radioactive compounds through the brain. In this way, a "map" is
created of the brain's changing blood flow and chemistry as a person
thinks and feels. |
Two of the most compelling
features of the last twenty years have been dramatic achievements in
the laboratory and striking advances in biomedical technology.
Together, they have literally extended the frontiers of the mind by
embodying emotions in the biology of the brain more successfully
than ever before and by creating the possibility of identifying the
intricate interconnections between brain-based emotions and the
functioning of the neuroendocrine and immune systems. Spectacular
developments in laboratory science and visualization technology have
been essential components of the explosive development of
neuroscience, a field which has quickly become one of the most
respected, exciting and actively pursued in medicine.67
Within the neurosciences an area variously called
"psychoneuroimmunology" and "neuroimmunomodulation"68
has recently emerged which seems on the verge of tracing the
pathways between emotions and disease whose connections had long
been glimpsed in clinical contexts by physicians ranging from Galen
to Freud and from Maimonides to Alexander.
The modern grounding of
emotional expression in the biology of the brain began with the work
of the American neuroanatomist James Papez. In 1937, Papez argued
from anatomical and clinical evidence that an "ensemble of
structures" in the lower, subcortical areas of the brain constituted
the "anatomic basis" and "harmonious mechanism" for the elaboration
and expression of emotions. Rejecting the possibility that emotion
is "a magic product," Papez insisted that it is "a physiologic
process which depends on an anatomic mechanism."69
Papez’s ideas were effectively promoted by Paul MacLean, a physician
and neurophysiologist. In 1949, MacLean proposed a hypothesized
"visceral brain" as an anatomical and functional system intermediate
between the "intellectual" cortex and the "discharging"
hypothalamus. This system was "largely concerned with visceral and
emotional functions."70
In the 1950s, MacLean generalized his ideas into a theory of the
"limbic system," an integrated set of subcortical structures in the
brain including the hippocampus and amygdala whose precise role in
emotional expression and modulation he explored through the
electrical and chemical stimulation of specific anatomical regions
and structures.71
Other investigators added human clinical evidence and the results of
surgery on the brains of laboratory animals, which also pointed to
the role of the limbic system in the expression of
emotions. |
An
overactive amygdala
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The organs of the immune system (thymus, spleen,
and lymph nodes) and the organs of the neuro-immune system (adrenal
gland, hypothalamus, and the cortical and subcortical brain).
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Interest in the limbic system
remained strong through recent times, although in the last several
years neuroscientists have raised questions about the looseness of
some of the earlier theoretical assumptions and anatomical
constructs. They are still interested in the neural substrates of
emotion within the brain but have shifted their attention to the
hemispheres of the cerebral cortex and to the interactions between
cortical and subcortical regions. In the 1970s, neuroscientists
began to concentrate on the right cortical hemisphere as the most
interesting locus of emotional control.73
Roger Sperry’s award of the Nobel Prize in 1981 for his work on
"cerebral laterality" (the differences between the "left" and the
"right" brain and their behavioral significance) reinforced this
trend, but respected neuroscientist R.W. Doty indicated in a 1989
review article that "any idea of emotion in an intact mammal being
played out purely via subcortical circuitry is an unsustainable
abstraction. On the other hand, the evidence is unequivocal that
subcortical structures are essential for the expression of the more
"primitive" emotions, and can support such expression in the absence
of the neocortex."74
Current work is verifying the integrative functioning of cortical
and subcortical areas (especially the amygdala) in the organism’s
response to primitive emotional experiences such as fear.75
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Using PET
scans, scientists are in the first stages of relating different
emotional states--pleasure, sorrow--to different patterns of brain
activity.
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Functional
magnetic resonance . imaging, or MRI, is another new technology
that can detect the living brain at work. This is a
computer-enhanced fMRI scan of a person who has been asked to look
at faces. The image shows increased blood flow in the part of the
visual cortex that recognizes faces.
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Powerful new imaging
techniques have supported and made possible the recent emphasis on
the anatomical substrates of emotion. 76
The most impressive techniques are computer assisted tomography (CAT
scans), magnetic resonance imaging (MRI), positron emission
tomography (PET scans), single-photon emission computed tomography
(SPECT), and functional magnetic resonance imaging (fMRI). The
breakthrough technology was computer assisted tomography, developed
in the 1960s and 1970s, for which Allan Cormack and Godfrey
Hounsfield received the Nobel Prize in 1979. The basic principle was
the computer synthesis of a three-dimensional image from a series of
two-dimensional "slices" taken at multiple angles (tomography) of
some signal aimed at or emanating from the patient and detected
outside his or her body. This principle was applied first to CAT
scans where the measured property was an x-ray attenuation
coefficient. The same principle was then applied to MRI imaging and
PET scans, where the measured property was natural magnetization
density in the first case and the concentration of an intravenously
injected radioisotope in the second. 77
The newer fMRI is based on the tomographic construction of images
formed by the signal differences between MRIs taken of the brain in
functionally activated and non-activated states. 78
CAT scans and MRI images are now widely used in clinical settings to
determine anomalies in cerebral anatomy. SPECT, PET and fMRI are
valuable tools, at this point employed primarily in research
settings to determine physiological and biochemical variations in
brain activity, including anatomically-localized alterations in
metabolism and neurochemical functioning which are visualized as
they occur. 79
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Optical
imaging camera
The optical
imaging camera allows scientists to peer even more deeply into the
brain, making pictures of nerve cells working together in ensembles.
A bright light shone onto the brain reflects backchanges in nerve
cells activity (measured through changing colors related to water
content, cell size, and amount of oxygen in the blood). These are
then turned into colorful images.
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Computerized
photomicrographic imaging
New technologies, like computerized
photomicrographic imaging, are bringing even the microscope world of
cells and genes more fully into the light of day.
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Many of the achievements in
the neurosciences have come at the intersection of this new imaging
technology with recent breakthroughs in neurochemistry.80
As one of neurochemistry’s leaders, Solomon Snyder, has said, "The
glue that has brought together findings from so many different
disciplines into a coherent concept of brain function is chemistry.
Indeed the revolution is more precisely characterized as a
revolution in ‘molecular neuroscience.’"81
Twenty years ago, Snyder was
among those neurochemists who succeeded in identifying opium-like
molecules in the brain (variously called "enkephalins,"
"endorphins," or sometimes just "endogenous opioids") that helped
regulate the sensation of pain. Endogenous opioids are a type of
"neurotransmitter," a long-studied class of biochemical substances
that convey messages from nerve fiber endings to other biological
receptors, whether nerve, muscle or gland. Neurochemists were able
to identify specific opiate "receptor sites" where the endogenous
opioids normally attach but at which they are sometimes displaced by
exogenous competitors such as morphine. Using photographic
techniques that take pictures of samples incorporating radioactive
materials and high power microscopy, scientists found large
concentrations of these receptor sites in areas of the brain (in the
limbic system) specifically associated with pain perception and
other forms of emotional regulation.82
More recently and with the help of PET scan and fMRI technology,
neuroscientists have been able to confirm the dense distribution of
opiate receptors in the structures of the limbic system and
especially in the amygdala. Neuroscientists thus seem to be closing
in on both the biochemical mechanisms and the anatomical
architecture of emotional expression in specific structures of the
brain. |
![5f525.gif](pst151_files/5f525.gif) |
Neurotransmitters
Different parts of your brain share information and organize plans
for action through a code system that involves both chemistry and
electricity. Chemicals called neurotransmitters" are emptied from
tiny sacs into the space between nerve cells. These chemicals cross
that space and bind to receptors on other nerve cells. The binding
process triggers an electrical stimulus in the receiving cells, that
starts the whole process of chemical release all over again.
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In perhaps the most exciting
development of all, a new field has emerged which is starting to
combine the latest in the neurosciences with the latest in
immunology to provide the scientific basis for understanding
relationships between emotions and disease once explored only in
clinical settings. Not yet possessing a generally agreed upon name,
this new field has been able to demonstrate previously unsuspected
but now verifiably direct connections between the immune system and
the neuroendocrine system. The field developed in two waves. The
first wave, rising in the late seventies and early eighties, was
generally called "psychoneuroimmunology" (PNI). Its roots could in
some sense be traced back to the pioneering studies of the Russian
immunologist S. Metal’nikov at the Pasteur Institute in Paris in the
1920s and 1930s and to the considerable work in the Soviet Union
from the 1920s through the 1950s on psychologically conditioned
immunobiological effects. The field really began to take shape
around 1980 under the combined leadership of the Americans George
Solomon, Novera Herbert Spector and Robert Ader, the Swiss Hugo
Besedovsky, and the Russian Elena A. Korneva. 83
Although each of these leaders came from a different discipline and
contributed different specific expertise (Ader, for example, was an
experimental psychologist, Solomon was a psychiatrist and Besedovsky
was an endocrinologist), they all agreed on the need to break down
the barriers that until then had artificially separated immunology
as a field from endocrinology and the neurosciences. As Ader and his
colleagues put the point in 1987, "In our view, the attempt to
understand immunity as an adaptive process that is independent of
and can be studied in isolation from other integrated adaptive
processes is, in its extreme form, a restrictive and restricting
paradigm." 84
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Activation
of T-cells
When a foreign toxin or bacteria, called an
antigen, enters the body, immune system cells race to the site of
invasion. These cells are called lymphocytes (T and B cells) and
macrophages. Receptors on the surface of these cells recognize and
bind to the invader. The binding process triggers the production of
chemical signals called interleukins. Interleukins allow immune
cells to mature, communicate with each other, and to make antibodies
and other substances that remove the invader. |
At the same time that interleukins (sometimes
called lymphokines and monokines) allow immune cells to signal one
another, they also allow immune cells to signal the brain--and vice
versa. |
Beginning in the late 1980s,
the second wave was marked by the recruitment of molecular
neuroscientists. This phase does not yet have a fixed name, although
"neuroimmunomodulation" (NIM) is widely accepted, while some leaders
prefer simply "neuro-immune interactions." Some of the scientists
recruited to the field during this phase were wary of PNI and
remained skeptical until they were persuaded by "harder" evidence
that the immune and neuroendocrine systems are in fact in close and
bi-directional communication and, indeed, "talk" to each other all
the time. A short list of discoveries early in the second wave
includes the following: demonstration of direct microanatomical
contacts between the nervous and the immune systems discovery that
anatomical lesions in or the electrical stimulation of parts of the
brain influence antibody production in the spleen and lymph nodes;
identification of receptor sites for neuroendocrine hormones and
neurotransmitters on cells of the immune system. The "clincher" was
the repeated proof in several different animal models that
interruptions of these communications on a genetic, surgical, or
pharmacological basis, lead to increased susceptibility to
inflammatory diseases like arthritis. The converse is now also being
shown, that too much responsiveness of these systems leads to
enhanced susceptibility to infection. Now it is certain that
particular molecules of the immune system (cytokines or
interleukins) signal areas of the brain directly as well as exert
influences on peripheral parts of the nervous system such as the
vagus nerve. This rigorously demonstrated "cross-talk" between the
immune and neuroendocrine systems has won over neuroscientists and
gained converts among the immunologists themselves. Even more
important, it provides the scientific basis for understanding--at
long last--how emotions can in fact influence the onset, course, and
remission of disease. |
Two very different signs of
enthusiasm and "arrival" already mark the 1990s: the inclusion of an
entry on "Neuroendocrine Regulation of Immunity" in the 1992
Encyclopedia of Immunology 85
and the featuring of psychoneuroimmunolgy as a central theme in Bill
Moyers's 1993 best seller, Healing and the Mind. 86
The first indicated the acceptance of the new field within the
mainstream of previously resistant immunology and the second
demonstrated popular fascination with the emerging inter-discipline.
Moyers and many of his readers seized upon the new field as seeming
to validate long-suspected but frequently denied connections between
emotions and disease. A spate of high-level international scientific
conferences marked by unusual energy and bold proclamations have
added to the sense of excitement. The proceedings of one of these
was published in 1994 as volume three of the "Hans Selye Symposia on
Neuroendocrinology and Stress." 87
The editors of the Selye volume capture the current mood:
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The
interaction of the nervous, endocrine and immune systems is only now
being considered seriously. This field represents a novel,
multidisciplinary approach in Biological Sciences. Even the name of
the field has not been settled as yet and there are debates going on
with regards to the proper term. . . . Modern science is equipped
with powerful research tools which make it feasible to advance
quickly in this complex multidisciplinary field, with the aim of
understanding the whole organism, rather than trying to analyze
restricted areas. The developments are spectacular, indeed, and the
new insights gained . . . have already advanced our understanding of
certain human diseases, such as autoimmune disease, inflammatory
diseases, nervous and endocrine abnormalities and the influence of
behavioral factors and of aging on the immune response and disease.
We sincerely hope this volume will contribute to the understanding
and acceptance of this brave new area of scientific enquiry.
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It may be that this "brave
new area" will finally validate long held beliefs about emotions and
disease that we in the West have been grappling with for at least
two millennia. |
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